Induction of a DNA adduct detectable by 32P-postlabeling in the dorsolateral prostate of NBL/Cr rats treated with estradiol-17{beta} and testosterone

Treatment with estradiol-17ß and testosterone inducesepithelial dysplasia and, subsequently, adenocarcinoma in thedorsolateral prostate of NBL rats. The purpose of this studywas to determine whether this carcinogenic effect is mediatedby genotoxicity. Analogous to adducts produced by estrogensin the male hamster kidney, a target of estrogen carcinogenicity,induction of DNA adducts detectable by ³²P-postlabeling wasinvestigated in the prostate target tissue. NBL rats were treatedwith separate Silastic tubing implants containing testosteroneand estradiol-17ß. Control animals received emptyimplants. Animals were killed at 8, 16 and 24 weeks after initiationof treatment, and accessory sex glands were sampled for adductanalysis. DNA of the dorsolateral and ventral prostate and thecoagulating gland (= anterior prostate) was isolated and analyzedby nuclease Pl-enhancement of the ³²P-postlabeling assay. DNAadducts were quantitated by Cerenkov counting. An adduct occurredselectively in DNA of the dorsolateral prostate of rats treatedwith estradiol plus testosterone for 16 or 24 weeks with relativeadduct level values of